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Clinical Insights and Emerging Strategies in Chronic Pain Management

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Anesthesiology".

Deadline for manuscript submissions: closed (20 February 2026) | Viewed by 4693

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Special Issue Editor

Prof. Dr. Cheol Lee

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Guest Editor

Department of Anesthesiology and Pain Medicine, Wonkwang University School of Medicine, 895 Muwang-ro, Iksan-si 54538, Republic of Korea
Interests: critical care medicine; chronic pain; pain management

Special Issue Information

Dear Colleagues,

Chronic pain remains a significant public health concern, and profoundly affects individuals' physical, emotional, and social well-being. This Special Issue focuses on advancements in our understanding and management of chronic neuropathic pain, with an emphasis on innovative diagnostic approaches, patient stratification, and interdisciplinary treatment strategies. Key areas of interest include the role of digital health tools, real-world evidence, and the comparative effectiveness of multimodal pain management models, particularly in conditions such as fibromyalgia, postherpetic neuralgia, and complex regional pain syndrome. We aim to compile contributions from diverse clinical disciplines in order to address early diagnosis, optimize long-term outcomes, and explore emerging therapies, including neuromodulation and pharmacological interventions. This Special Issue seeks to provide actionable insights for clinicians and researchers, fostering a collaborative dialogue that shapes the future of chronic neuropathic pain management.

Prof. Dr. Cheol Lee
Guest Editor

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Keywords

chronic pain
neuropathic pain
multimodal pain management
digital health
real-world evidence
interdiscipli-nary care

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Published Papers (4 papers)

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Research

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36 pages, 2092 KB

Open AccessArticle

Self-Efficacy as a Central Mediator of Pain, Function, and Depression: Insights of a Cross-Sectional Analysis of Depersonalized Data from the German Pain e-Registry

by Michael A. Überall, Philipp C. G. Müller-Schwefe, Jan-Peter Jansen, Michael A. Küster, Ingo Ostgathe and Jens Kuhn

J. Clin. Med. 2026, 15(8), 3061; https://doi.org/10.3390/jcm15083061 - 17 Apr 2026

Viewed by 381

Abstract

Background: Depression is highly prevalent among individuals with chronic pain and strongly impacts pain intensity, psychological functioning, and health-related quality of life. Self-efficacy has emerged as a potentially modifiable resilience factor within this interplay, yet large-scale real-world evidence integrating self-efficacy into multidimensional pain–depression models remains limited. Methods: This cross-sectional registry-based analysis evaluated standardized patient-reported measures from chronic pain patients enrolled in the German Pain e-Registry. All variables were directionally harmonized and transformed into standardized deviation scores (hSDSs) relative to patients without depression. Group-level hSDS profiles for five DASS-21 depression severity strata (none, mild, moderate, severe, extreme) were compared across pain intensity, disability, psychological well-being, affective pain processing, quality of life, neuropathic pain features, and pain-related self-efficacy (PSEQ). Correlations and exploratory principal component analysis (PCA) were used to assess multivariate structure. PCA-informed path models were estimated to evaluate directional relationships between pain, function, depression, and self-efficacy. All directional and mediation models represent exploratory, theory-informed statistical frameworks and do not imply causal or mechanistic relationships. Results: Across all domains, hSDS values increased monotonically with depression severity, while self-efficacy showed the strongest inverse gradient. Exploratory PCA revealed a dominant severity component explaining most variance and a secondary affective–self-efficacy axis, supporting the conceptual separation between functional–physical and psychological–affective symptom clusters. In the bottom-up path model (pain → function → self-efficacy → depression), self-efficacy showed the largest indirect statistical contribution within the proposed path models, and the model explained 55% of depression variance (R² = 0.55). In the top-down model (depression → affective pain → self-efficacy → pain), 45% of pain intensity variance was explained (R² = 0.45), again with self-efficacy as a central mediating construct. Associations remained robust after adjustment for age, sex, and BMI, as well as during sensitivity analyses. Conclusions: This large real-world cohort demonstrates a highly coherent pattern of associations across biopsychosocial domains and highlights pain-related self-efficacy as a central statistical construct linking pain, functional impairment, and depressive symptom burden within the applied exploratory models. The findings suggest that self-efficacy occupies a key position in the interplay between pain and mood, and that pharmacological and non-pharmacological treatments traditionally used in chronic pain management may be associated with changes in this construct. Importantly, all directional and mediation analyses are exploratory and do not imply causal or mechanistic relationships. Therapeutic strategies aimed at enhancing self-efficacy may therefore represent promising targets for future research within multimodal pain management frameworks. Full article

(This article belongs to the Special Issue Clinical Insights and Emerging Strategies in Chronic Pain Management)

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20 pages, 3039 KB

Open AccessArticle

Treatment Persistence in Migraine Prophylaxis Comparing CGRP Monoclonal Antibodies vs. High-/Low-Evidence Conventional Oral Preventives—A Comparative Real-World Evidence Study of Depersonalized Data of the German Pain e-Registry

by Michael A. Überall, Philipp C. G. Müller-Schwefe, Michael A. Küster and Jan-Peter Jansen

J. Clin. Med. 2026, 15(5), 1985; https://doi.org/10.3390/jcm15051985 - 5 Mar 2026

Cited by 1 | Viewed by 686

Abstract

Background/Objectives: Real-world persistence of traditional oral migraine preventive medications is low in routine care. Prior large claims-based analyses demonstrated early discontinuation of oral prophylaxis, but such datasets neither included modern preventive options such as monoclonal antibodies (mAB) against calcitonin-gene-related peptide (CGRP), nor were able to capture clinically validated reasons for discontinuation. The primary aim was to compare real-world treatment persistence and discontinuation reasons due to adverse drug reactions (ADRs) or insufficient efficacy among three preventive therapy classes: subcutaneous CGRP mAB and oral high- (HEVP) and low-evidence preventive medications (LEVP). A secondary aim was to examine persistence patterns of individual substances within the HEVP cohort. Methods: This exploratory observational study used depersonalized real-world data from the German Pain e-Registry (GPeR), a national multicenter clinical registry. Persistence trajectories were evaluated over six months, together with cumulative proportions of ADR-related and inefficacy-related discontinuations. Pairwise comparisons across the three cohorts based on chi-square analyses, odds ratios, relative risks, effect sizes, and numbers needed to harm. Results: At six months, persistence was highest for CGRP monoclonal antibodies at 89.4%, compared with 43.0% for LEVP and 34.0% for HEVP (all p < 0.001). ADR-related discontinuation occurred in 7.0% with CGRP vs. 35.7/44.5% with LEVP/HEVP, and discontinuations due to insufficient efficacy occurred in 3.6% with CGRP vs. 21.3/21.5% with LEVP/HEVP, without influence of sex or migraine frequency. Substance-level analysis within HEVP showed the steepest early attrition for tricyclic antidepressants, followed by beta-blockers, with comparatively more favorable though still suboptimal persistence for topiramate and flunarizine. Conclusions: Real-world treatment persistence is markedly higher with CGRP mAB than with HEVP/LEVP. Oral preventives show high discontinuation rates due to both ADR and insufficient efficacy, indicating substantial limitations in real-world applicability. These findings highlight the clinical relevance of a modern mechanism-based migraine prevention with CGRP mAB. Full article

(This article belongs to the Special Issue Clinical Insights and Emerging Strategies in Chronic Pain Management)

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11 pages, 535 KB

Open AccessArticle

Comparison of Pulsed Radiofrequency and Endoscopic Piriformis Release for Refractory Piriformis Syndrome: A Propensity Score-Matched Retrospective Cohort Study

by Eunsung Park, Duyoung Choi and Cheol Lee

J. Clin. Med. 2025, 14(16), 5908; https://doi.org/10.3390/jcm14165908 - 21 Aug 2025

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Abstract

Background/Objective: Piriformis syndrome (PS) causes sciatic nerve entrapment and chronic pain. In refractory cases, pulsed radiofrequency (PRF) and endoscopic piriformis release (EPR) are used, but comparative evidence is limited. Methods: This retrospective cohort study compared PRF and EPR in patients treated from 2018 to 2024 at a tertiary hospital using propensity score matching (PSM). Patients with PS, unresponsive to conservative treatment (≥3 months), were included. PRF targeted the sciatic nerve under imaging guidance; EPR involved endoscopic decompression. Primary outcomes were Numeric Rating Scale (NRS) scores at 3 and 6 months. Secondary outcomes included patient satisfaction, reintervention rates, complications, and the Oswestry Disability Index (ODI), where available. After PSM, 115 patients were analyzed per cohort. Multivariate regression identified the predictors of pain improvement. Results: From 465 eligible patients (PRF 350; EPR 115), after PSM, 230 patients were analyzed (115 per cohort). The baseline NRS score was 7.4 ± 1.4 (PRF) vs. 7.5 ± 1.3 (EPR). At 3 months, EPR showed a lower NRS score (2.6 ± 1.3) compared to PRF (3.2 ± 1.6; p = 0.032). At 6 months, the EPR NRS score was 2.2 ± 1.1 vs. 2.9 ± 1.5 for PRF (p = 0.018). EPR had a higher rate of ≥50% NRS score reduction (78% vs. 65%; p = 0.041). EPR patients reported higher satisfaction and fewer reinterventions but more complications. Regression analysis identified EPR (OR = 2.15), higher baseline NRS scores, and shorter symptom duration as predictors of improvement. Conclusions: EPR provided superior pain relief compared to PRF at 3 and 6 months, although with a higher risk of complications. PRF remains a safer initial option. Full article

(This article belongs to the Special Issue Clinical Insights and Emerging Strategies in Chronic Pain Management)

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Review

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21 pages, 1333 KB

Open AccessReview

Repurposed Systemic Pharmacologic Agents in Chronic Pain: Emerging Mechanistic and Clinical Insights

by Alyssa McKenzie, Rachel Dombrower, Tiffany G. Bittar, Sophia M. McKenzie, Nitchanan Theeraphapphong, Neil Shukla, Hatim Hussain and Alaa Abd-Elsayed

J. Clin. Med. 2026, 15(4), 1572; https://doi.org/10.3390/jcm15041572 - 17 Feb 2026

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Abstract

Chronic pain is a multisystem disorder involving neuroimmune activation, metabolic dysregulation, mitochondrial dysfunction, and alterations in autonomic and sensory signaling, leading to peripheral and central sensitization, reduced responsiveness to standard analgesics, and persistent symptoms. Growing evidence suggests that several widely used systemic drugs, initially developed for metabolic, cardiovascular, immunological, or neurological conditions, interact with biological mechanisms involved in pain pathophysiology. This narrative review examines the mechanistic and emerging clinical evidence describing how systemically administered pharmacological agents interact with pathways implicated in chronic pain, focusing on glucagon-like peptide-1 receptor agonists, sodium–glucose cotransporter-2 inhibitors, metformin, statins, minocycline, ibudilast, low-dose naltrexone, beta-blockers, and cannabinoids. The mechanisms reviewed include glial activation, cytokine signaling, oxidative stress, mitochondrial dysfunction, ion channel sensitization, and autonomic imbalance. The use of these systemic agents may provide additional treatment options for patients with chronic neuropathic, centralized, or mixed pain states who have limited response to conventional therapies, although current clinical evidence remains preliminary. Full article

(This article belongs to the Special Issue Clinical Insights and Emerging Strategies in Chronic Pain Management)

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